Breast cancer affects over 120,000 women each year in the USA. An increasing number of these women present with early stage disease for which surgery alone is curative for most patients. Unfortunately, a significant number of patients do relapse. Adjuvant chemotherapy has been demonstrated to be effective in reducing relapse. There currently exists no reliable method to differentiate those patients that would benefit from adjuvant therapy from those cured by surgery. The aim of this proposal is to identify molecular markers of cancer cells that have increased malignant potential. To this end the investigators have used the realtionshop between erbB-2 and EGF receptor overexpression and increased malignancy to screen for new molecular markers of malignancy. In Phase I they demonstrated that cDNA clones can be isolated that are expressed in association with erbB-2 and EGF receptor gene expression. These candidate markers of malignancy are expressed in primary breast CA specimens and cell lines that overexpress erbB-2 and EGF receptor but in some other samples as well. These data are consistent with an improved marker of malignancy. In Phase II they will test the utility of these candidate markers for the improved diagnosis and determination of prognosis of breast CA. This will be accomplished by molecular characterization of the cDNAs, development of the antibodies to the corresponding protein, and immunohistochemical analysis of a large retrospective group of patient samples.